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* = Presenting author

P012 MAIT cell activation reflects mucosal inflammation in ulcerative colitis

K. Haga*1, A. Chiba2, T. Shibuya1, T. Osada1, D. Ishikawa1, T. Kodani1, O. Nomura1, S. Watanabe1, S. Miyake2

1Juntendo University, Department of Gastroenterology, Tokyo, Japan, 2Juntendo University, Department of Immunology, Tokyo, Japan

Background

Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory disorder of the large intestine. Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and UC result from a dysregulated response of the mucosal immune system to components of the luminal microbiota, and the breakdown of immune tolerance in individuals who are genetically predisposed to the disease. Mucosal-associated invariant T (MAIT) cells are a member of innate-like lymphocytes found abundantly in the mucosal tissue. Studies have revealed that human MAIT cells are more abundant and constitute approximately 5% of peripheral blood T-cells, and MAIT cells are able to produce large amounts cytokines very rapidly upon activation. These findings suggest possible roles of these cells in various types of immune responses. In this study, we aimed to investigate the role of MAIT cells in patients with UC.

Methods

A total of 38 UC patients and 34 healthy subjects were included in this study. The frequency of MAIT cells, as well as the production of cytokines and expression levels of an activation marker by these cells in the peripheral blood of UC patients and healthy controls, were analysed by FACS LSR Fortessa with Flowjo software. We performed intracellular staining of cytokines in MAIT cells upon activation with PMA ionomycine. MAIT cells were identified as CD3+γδTCR-Vα7.2TCR+CD161–high cells. Additionally, MAIT cells were quantified in colon biopsies of UC patients using a confocal microscope.

Results

There was a significant reduction in MAIT cell frequency in the peripheral blood of UC patients compared with healthy controls (p < 0.0001). MAIT cells from UC patients secreted more IL-17 than healthy controls. The frequency of MAIT cells did not reflect the disease activity in UC patients; however, the expression levels of an activation marker on these cells were correlated with disease activity and endoscopic scores, as well as plasma levels of IL-18. Further, MAIT cells increased in the inflamed mucosa, and their frequency was correlated with clinical and endoscopical disease activity in UC patients.

Conclusion

This study demonstrated that MAIT cells were increased in the colon tissue of active UC patients and were activated in association with enhanced production of inflammatory cytokines in peripheral blood. In addition, there were positive correlations between the activation as well as frequency of MAIT cells in the inflamed colon and disease activity. The findings from this study indicate that MAIT cells may be associated with UC, and could be used as potential biomarkers or therapeutic targets in UC.